Coordinated lipid transfer between the endoplasmic reticulum and the Golgi complex requires the VAP proteins and is essential for Golgi-mediated transport
Coordinated lipid transfer between the endoplasmic reticulum and the Golgi complex requires the VAP proteins and is essential for Golgi-mediated transport
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DOI：
10.1091/mbc.e08-05-0498
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发表时间：
2008-09-01
影响因子：
3.3
通讯作者：
Lev, Sima
中科院分区：
文献类型：
--
作者：
Peretti, Diego;Dahan, Nili;Lev, Sima
胞内细胞器之间的脂质转运是由囊泡和非囊泡转运机制介导的，对于维持不同细胞膜的特性至关重要。在内质网（ER）和高尔基体复合体之间的非囊泡性脂质转运已被提出影响高尔基膜的脂质组成。在这里，我们发现完整的er膜蛋白VAP-A和VAP-B影响高尔基复合体的结构和功能完整性。RNA干扰导致VAPs耗竭，降低了高尔基膜中磷脂酰肌醇-4-磷酸（PI4P）、二酰基甘油和鞘磷脂的水平，并导致高尔基介导的运输事件的实质性抑制。这些作用是由脂质转移/结合蛋白Nir2、氧甾醇结合蛋白（OSBP）和神经酰胺转移蛋白（CERT）协调介导的，它们通过其FFAT基序与VAPs相互作用。VAPs对PI4P水平的影响是由磷脂酰肌醇/磷脂酰胆碱转移蛋白Nir2介导的，该蛋白是OSBP和CERT的高尔基靶向以及随后产生二酰基甘油和鞘磷脂所必需的。我们认为Nir2、OSBP和CERT在er -高尔基膜接触位点协同作用，从而影响高尔基膜的脂质组成，从而影响其结构和功能特性。
Lipid transport between intracellular organelles is mediated by vesicular and nonvesicular transport mechanisms and is critical for maintaining the identities of different cellular membranes. Nonvesicular lipid transport between the endoplasmic reticulum (ER) and the Golgi complex has been proposed to affect the lipid composition of the Golgi membranes. Here, we show that the integral ER-membrane proteins VAP-A and VAP-B affect the structural and functional integrity of the Golgi complex. Depletion of VAPs by RNA interference reduces the levels of phosphatidylinositol-4-phosphate (PI4P), diacylglycerol, and sphingomyelin in the Golgi membranes, and it leads to substantial inhibition of Golgi-mediated transport events. These effects are coordinately mediated by the lipid-transfer/binding proteins Nir2, oxysterol-binding protein (OSBP), and ceramide-transfer protein (CERT), which interact with VAPs via their FFAT motif. The effect of VAPs on PI4P levels is mediated by the phosphatidylinositol/phosphatidylcholine transfer protein Nir2, which is required for Golgi targeting of OSBP and CERT and the subsequent production of diacylglycerol and sphingomyelin. We propose that Nir2, OSBP, and CERT function coordinately at the ER-Golgi membrane contact sites, thereby affecting the lipid composition of the Golgi membranes and consequently their structural and functional identities.